OBJECTIVE To observe the clinical efficacy of donafenib combined with programmed death-1 （PD-1） inhibitors and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma （HCC）. METHODS This retrospective study included 165 patients with unresectable HCC who were treated at the Fourth and First Affiliated Hospitals of Soochow University between June 2022 and March 2023. Among them， 89 patients received PD-1 inhibitors （tislelizumab or sintilimab， similarly hereinafter） plus vascular intervention （control group） and 76 patients received donafenib in combination with PD-1 inhibitors and vascular intervention （observation group）. Short-term efficacy （3 months after treatment）， long-term efficacy （2 years after treatment）， the levels of liver function indexes [serum alanine amino-transferase （ALT）， aspartate transferase （AST）， and total bilirubin （TBil）] and tumor biomarkers [alpha fetoprotein （AFP）， carcinoembryonic antigen （CEA）， carbohydrate antigen 19-9 （CA19-9）， and des-gamma-carboxy prothrombin （DCP）] before treatment and after 3 months of treatment， as well as the occurrence of adverse drug reaction （ADR） during treatment， were compared between the two groups. In addition， overall response rate （ORR） stratified by PD-1 inhibitor type was analyzed. RESULTS After treatment， the ORR was significantly higher in the observation group than in the control group （P＜0.05）； although the disease control rate was higher in the observation group compared to the control group， the difference was not statistically significant （P＞0.05）. The median overall survival of patients in the observation group was 16.9 months [95% confidence interval （CI）： 14.2 to 19.1 months]， which was significantly longer than that in the control group （12.4 months， 95%CI： 10.1 to 15.3 months） （P＜0.05）. Subgroup analysis result indicated that therapeutic advantage was consistent across both sintilimab and tislelizumab subgroups， with no significant heterogeneity （P＞0.1， I 2＜0.001%）. Before treatment， there were no significant differences in liver function indexes or tumor marker levels between 2 groups （P＞0.05）. After treatment， both groups showed significant declines in these indicators compared with baseline （P＜0.05）， with greater reductions observed in the observation group （P＜0.05）. There were no statistically significant differences in overall incidence of ADR and grade ≥3 ADRs between the two groups （P＞0.05）. CONCLUSIONS For patients with unresectable HCC， the combination of donafenib， PD-1 inhibitors and vascular intervention therapy may achieve superior clinical outcomes without increasing the risk of treatment-related ADR.

Objective:To conduct a survey of the current status of education service offered to professional master's students in clinical medicine in a grade-A tertiary hospital in Chongqing, China based on the SERVQUAL model, and to discuss the problems with education service as well as measures for improvement.Methods:Based on the SERVQUAL model, a questionnaire consisting of 30 items in 5 dimensions was designed. Each item was rated for an expected score and a perceived score. Medical professional master's students in a Chongqing grade-A tertiary hospital in the first half year of 2022 were surveyed for the expected and perceived quality of education service to calculate service quality (SQ). SPSS 26.0 was used for reliability and validity analyses and descriptive statistical analyses. The results were analyzed using a two-dimensional quadrant graph.Results:A total of 263 valid questionnaires were returned, with an effective response rate of 97.77%. For both the expectation scale and the perception scale, the Cronbach's α values were >0.8, and the Kaiser-Meyer-Olkin values were >0.7, indicating good reliability and validity. The mean expected value of education service quality was 4.28, the mean perceived value was 3.96, and the mean gap value was -0.32. The SQ scores for all the items were negative, except for "provide neat suits for work". The two-dimensional quadrant analysis showed that 6 items were located in quadrant III (low-expectation and low-perception area), and 7 items were located in quadrant IV (high-expectation and low-perception area).Conclusions:The evaluation scale based on the SERVQUAL model can effectively reflect problems in postgraduate education for medical master's students, helping develop strategies to improve the quality of education service.

Aim To investigate the effects of bone-forming protein BMP9 on aerobic glycolysis,migration and invasion ability in triple-negative breast cancer MDA-MB-231 cells and the underlying mechanisms.Methods The experimental group infected MDA-MB-231 cells with human BMP9 recombinant adenovirus(AdBMP9),while the control group infected cells with empty GFP adenovirus.Lactate,glucose and ATP as-say kits were used to detect glucose uptake,lactate and ATP production.The correlation between BMP9 and key glycolytic enzyme genes in pancarcinoma was ana-lyzed using GEPIA2 database.The mRNA expression levels of GLUT1,HK2,PKM2 and LDHA in MDA-MB-231 cells after overexpression of BMP9 were detec-ted by qRT-PCR.Potential targets of BMP9 inhibiting MDA-MB-231 aerobic glycolysis were analyzed in STRING database.The expression levels of HIF-1αand downstream protein were detected by Western blot.The changes of cell migration and invasion ability after different treatments were evaluated by the scratch heal-ing assay and Transwell assay.Results Compared with the control group,BMP9 down-regulated glucose uptake,lactate production,ATP level(P＜0.01),and inhibited HIF-1α and its downstream protein ex-pression in MDA-MB-231 cells.Overexpression of HIF-1α in rescue experiment reversed the inhibitory effect of BMP9 on aerobic glycolysis,migration and in-vasion of MDA-MB-231 breast cancer cells.Conclu-sion BMP9 down-regulates HIF-1α to inhibit the aer-obic glycolysis and migration and invasion ability of MDA-MB-231 breast cancer cells.

Aim To explore the effects of sirolimus on the growth and development of motor,vascular,nerv-ous,and immune systems through zebrafish models.Methods After 3 hours of fertilization of zebrafish embryos,different concentrations of sirolimus were add-ed to the growth environment,and the growth and de-velopment of the embryos was recorded.Transgenic ze-brafish models labeled with blood vessels,nerves or im-mune cells were used to compare the drug effects on the growth and development of those systems.Results At the concentration of 0.5 μmol·L-1,the hatching rate and the body length(P＜0.01)were significantly smaller than those of the control group,and movement was also significantly slowed down.Meanwhile,the length of axons of the nervous system,the development of intersegmental vessels,and the growth of immune cells were significantly delayed by drug treatment.But when the concentration was below 0.1 μmol·L-1,there was no statistically difference between the control group and the sirolimus group.Conclusions When the concentration of sirolimus exceeds a certain level,it can significantly slow down the growth and development of movement,blood vessels,nervous system and im-mune system of zebrafish.Therefore,in clinical prac-tice,it is important to monitor the blood concentration of sirolimus in children on time.

Objective To study the application value of different transbronchial biopsies in the diagnosis of central lung cancer in elderly patients.Methods The clinical data of 97 elderly patients with central lung cancer diagnosed by pathology from June 2020 to June 2023 in the 923rd Hospital of Chinese People's Liberation Army Joint Logistic Support Force were retrospectively analyzed.According to the different initial transbronchial biopsy methods,the patients were divided into the endobronchial biopsy(EBB)group(n=51)and the conventional transbronchial needle aspiration(cTBNA)group(n=46).The histopathological results were statistically analyzed,and the first biopsy positive rates of EBB and cTBNA in the diagnosis of senile central lung cancer were calculated and compared.At the same time,the differences of biopsy tolerance and complications between the two groups were evaluated.Results The squamous cell carcinoma proportions in both groups were over 50%.There was no significant difference in the first biopsy positive rate between the two groups(P>0.05).The incidence of temporary retreat of the scope due to subjective tolerance in the EBB group was higher than that in the cTBNA group,and the difference was statistically significant(P<0.05).There was a statistically significant difference in the incidence of intraoperative complications of different grades between the two groups(P<0.001).Among them,the incidence of grade 2 and above complications during surgery in the EBB group was significantly higher than that in the cTBNA group(P<0.001).Conclusion For elderly patients with central lung cancer,the success rate of the first biopsy of EBB and cTBNA is roughly equivalent,but the incidence of postoperative complications of the latter is significantly lower than that of the former.cTBNA can be used as the first biopsy method for this population.

Objective To investigate the effects of Jianpi Huatan Fang on lipid metabolism and expression levels of FOXO1 and PDK4 in rats with polycystic ovary syndrome(PCOS)and insulin resistance(IR).Methods Forty female rats were divided randomly into a blank control group(n=10)and a model group(n=30).A PCOS-IR rat model was established using a high-fat diet(8 weeks)combined with letrozole(added at weeks 4～8).Thirty successfully modeled rats were then divided randomly into a model control group,a Jianpi Huatan Fang group(11.07 g/kg),and a metformin group(0.2 g/kg)(n=10 rats per group).Drug intervention was given for 4 weeks.The general status,Traditional Chinese medicine syndrome score,and weight changes were observed in each group.Histopathological changes in the ovary were detected by hematoxylin and eosin staining.Fasting blood glucose and blood lipids were measured using a blood biochemical analyzer.Levels of sex hormones including follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),estradiol(E2),and insulin were determined by enzyme linked immunosorbent assay and changes in the expression of FOXO1 and PDK4 in the ovaries were determined by Western Blot and real-time fluorescence quantitative polymerase chain reaction.Results Rats in the model control group exhibited symptoms of spleen deficiency and phlegm-dampness and showed significant weight gain,sex hormone disorders,polycystic ovarian changes,and dysregulation of glucose and lipid metabolism,compared with rats in the blank control group(P＜0.01).In addition,weight increase was slower in rats in the Jianpi Huatan Fang group and the metformin group compared with that in the model control group,and follicle development was improved.Serum LH,T,LH/FSH,fasting blood glucose,insulin,homeostatic model assessment for IR,cholesterol,triglycerides,and low-density lipoprotein cholesterol decreased,estradiol and FSH increased,and ovarian FOXO1 and PDK4 mRNA and protein expression levels were down regulated in the Jianpi Huatan Fang group compared with the findings in the model control group(P＜0.05,P＜0.01).Serum high-density lipoprotein cholesterol content was also increased,but the difference was not significant(P＞0.05).Conclusions Jianpi Huatan Fang can effectively regulate sex hormone secretion,improve ovarian reproductive function,and regulate glucose and lipid metabolism in obese PCOS-IR rats,possibly via inhibiting the FOXO1/PDK4 pathway.

Objective:To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia(CLL).Methods:The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively.Results:The median age of 59 CLL patients was 60.5(36-78).After one year of BTKi treatment,the CLL clones(CD5+/CD19+)of 51 cases(86.4％)were significantly reduced,in which the number of cloned-B cells decreased significantly from(46±6.1)× 109/L to(2.3±0.4)× 109/L(P=0.0013).But there was no significant change in the number of non-cloned B cells(CD19+minus CD5+/CD19+).After BTKi treatment,IgA increased significantly from(0.75±0.09)g/L to(1.31±0.1)g/L(P＜0.001),while IgG and IgM decreased from(8.1±0.2)g/L and(0.52±0.6)g/L to(7.1±0.1)g/L and(0.47±0.1)g/L,respectively(P＜0.001,P=0.002).BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients,which manifested as both a decrease in total number of T cells from(2.1±0.1)× 109/L to(1.6±0.4)× 109/L and NK/T cells from(0.11±0.1)× 109/L to(0.07±0.01)× 109/L(P=0.042,P=0.038),both an increase in number of CD4+cells from(0.15±6.1)× 109/L to(0.19±0.4)× 109/L and CD8+cells from(0.27±0.01)× 109/L to(0.41±0.08)× 109/L(both P＜0.001).BTKi treatment also up-regulated the expression of interleukin(IL)-2 while down-regulated IL-4 and interferon(IFN)-γ.However,the expression of IL-6,IL-10,and tumor necrosis factor(TNF)-α did not change significantly.BTKi treatment could also restored the diversity of TCR and BCR in CLL patients,especially obviously in those patients with complete remission(CR)than those with partial remission(PR).Before and after BTKi treatment,Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001(P＜0.001),while in patients with PR was 0.01±0.03 and 0.05±0.02(P＞0.05),respectively.Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15(P＜0.001),while in patients with PR was 0.15±0.009 and 0.23±0.18(P＜0.05),respectively.Conclusions:BTKi treatment can shrink the clone size in CLL patients,promote the expression of IgA,increase the number of functional T cells,and regulate the secretion of cytokines such as IL-2,IL-4,and IFN-γ.BTKi also promote the recovery of diversity of TCR and BCR.BTKi treatment contributes to the reconstitution of immune function in CLL patients.

Objective:io investigate the expression level and clinical correlation of microRNA-144/451 gene cluster(miR-144/451)in different types of anemia.Methods:The peripheral blood of patients with aplastic anemia(AA),myelodysplastic syndrome(MDS)and diffuse large B-cell lymphoma(DLBCL)who had been diagnosed with anemia for the first time and after chemotherapy were collected.The expression levels of miR-144 and miR-451 were measured by RT-qPCR,and the correlation between the expression levels of miR-144 and miR-451 and routine laboratory indexes was analyzed by Spearman correlation analysis.Results:The expression levels of miR-144 and miR-451 in the peripheral blood of AA and MDS patients were significantly lower than those in normal controls(all P＜0.0 1).No statistical differences were observed in the expression level of miR-144 in three subgroups of DLBCL patients(P＞0.05),while the expression level of miR-451 in peripheral blood of three subgroups of DLBCL patients were significantly higher than those in normal controls(all P＜0.05).Correlation analysis showed that the expression levels of miR-144 and miR-451 in AA patients were positively correlated with red blood cell distribution width-coefficient of variation(RDW-CV)(r=0.629,0.574).There were no significant correlations between the expression levels of miR-144 and miR-451 and laboratory parameters in MDS and DLBCL patients.Conclusion:Different types of anemia disorders have varying levels of miR-144 and miR-451 expression,which is anticipated to develop into a secondary diagnostic and differential diagnostic indicator for clinical anemia diseases.

Objective:To analyze the intrauterine ultrasound manifestations and postnatal follow-up outcomes of fetuses with 2q13 microdeletion.Methods:This retrospective study involved 23 cases of 2q13 microdeletion, diagnosed via amniotic fluid chromosome karyotyping and single nucleotide polymorphism-array (SNP-array) following amniocentesis, between January 1, 2018, and September 1, 2022, at Wuxi Maternity and Child Health Care Hospital. Descriptive statistical analysis was applied to prenatal diagnostic indications, intrauterine ultrasound findings, prenatal diagnosis results, and postnatal follow-up outcomes.Results:(1) The prenatal diagnostic indications for the 23 cases of 2q13 microdeletion included seven cases (30.4%) of high-risk serological screening, six cases (26.1%) of increased nuchal translucency (NT), two cases (8.7%) of fetal heart defects, two cases (8.7%) of advanced maternal age, two cases (8.7%) of fetal choroid plexus cysts (one of which was also associated with high-risk serological screening), one case (4.3%) of suboptimal fetal nasal bone fusion, one case (4.3%) of non-invasive prenatal testing suggesting chromosomal abnormalities, one case (4.3%) of fetal obstructive polycystic kidneys, one case (4.3%) of fetal subependymal cysts, and one case (4.3%) of fetal growth restriction. (2) Intrauterine ultrasound findings included six cases (26.1%) of NT thickening, four cases (17.4%) of intrauterine growth restriction, two cases (8.7%) of fetal heart defects, two cases (8.7%) of choroid plexus cysts, one case (4.3%) of oligohydramnios, one case (4.3%) of suboptimal fetal nasal bone fusion, one case (4.3%) of short long bones in the fetus, one case (4.3%) of polyhydramnios with large fetal abdominal circumference, one case (4.3%) of large fetal abdominal circumference, short long bones, and subependymal cysts of the brain ventricles, and one case (4.3%) of fetal obstructive polycystic kidneys; the remaining six cases (26.1%) showed no abnormal ultrasound findings. (3) Chromosome karyotyping revealed three cases of chromosomal structural abnormalities, one case of sex chromosome numerical abnormalities, and the remaining 19 cases showed no abnormalities. Amniotic fluid SNP-array results indicated deletions ranging from 104 to 1 745 kb. Parental verification was performed in ten cases, showing maternal inheritance in four cases, paternal inheritance in five, and one case of a de novo mutation. (4) Four cases (17.4%) opted for pregnancy termination, while 19 cases (82.6%) resulted in live births. The 19 live-born children underwent telephone and child health follow-up, with ages at follow-up being 3 years (ranging from 9 to 58.8 months). Apart from two cases that did not undergo newborn congenital heart disease screening, the remaining 17 surviving infants were screened without any abnormalities. Five cases had abnormal growth and development during follow-up: one 18-month-old with mild language developmental delay, one 3-year-old plus 26 days with mild language developmental delay, one 18-month-old with language developmental delay, one 3-year-old with astigmatism, and one 30-month-old with refractive error in both eyes during a physical examination; the other 14 children showed no significant abnormalities in growth and development. Conclusions:The intrauterine ultrasound manifestations of fetuses with 2q13 microdeletion are non-specific, and most of them are inherited from their parents. Postnatal follow-up should pay attention to the development of the nervous system of children.

Objective:To identify the genetic causes of adverse pregnancy outcomes in five families and provide a basis for rational guidance on genetic and reproductive counseling.Methods:A retrospective analysis was conducted on five families with a history of adverse pregnancy outcomes, where one partner was found to have a cryptic balanced translocation. These cases were identified among pregnant women who underwent invasive prenatal diagnosis at the Department of Medical Genetics and Prenatal Diagnosis, Wuxi Maternity and Child Health Care Hospital, from January 2016 to June 2023. Conventional G-banding karyotyping and chromosomal microarray analysis (CMA) were performed on affected children/fetus samples. Chromosome G-banding and fluorescence in situ hybridization (FISH) were used for parental tracing. Genetic counseling was provided for all cases, and the pregnancy outcomes were followed up. Descriptive analysis was applied in this study. Results:Case 1 involved an eldest son with unexplained intellectual disability, and the CMA results showed an 8.6 Mb deletion in the 4p16.3p16.1 region and a 1.0 Mb duplication in the 7q36.3 region. Unbalanced translocations were detected in the current pregnancies of the other four cases, which were a 6.1 Mb duplication in the 14q32.2q32.33 region with a 1.6 Mb deletion in the 21q22.3 region (Case 2), a 10.8 Mb duplication in the 6q25.3q27 region with a 1.2 Mb deletion in the 15q26.3 region (Case 3), a 1.0 Mb duplication in the 5p15.33 region with a 2.9 Mb deletion in the 6q27 region (Case 4), and a 3.2 Mb deletion in the 1q44 region with a 4.8 Mb duplication in the 19p13.3 region (Case 5). FISH confirmed that either the husband or the wife in each of the five families was a carrier of a cryptic balanced translocation. Further CMA testing on amniotic fluid samples from previous terminated pregnancies of Cases 3 and 4 also indicated unbalanced translocations. Both the current pregnancy of Case 1 and the subsequent pregnancy of Case 2 gave birth to healthy babies after non-abnormal prenatal diagnosis and genetic counseling. Cases 3 to 5 are currently preparing for pregnancy.Conclusion:Advances and combined application of genetic technologies will be conducive to improving the diagnosis of cryptic balanced translocations in some families with adverse pregnancy outcomes, providing a sound basis for genetic counseling in future pregnancy.